Sandhoff Disease

Leiden, Netherlands, 09 January 2025 – Azafaros, a company focused on developing treatments for the unmet needs of patients with rare lysosomal storage disorders, today announced that it will present at J.P. Morgan’s 43rd Annual Healthcare Conference on Thursday, January 16, 2025. The company’s presentation will begin at 8:30 a.m. PT/11:30 am (Eastern Time). The presentation will focus on the company’s lead product, nizubaglustat, a potential treatment for rare lysosomal storage disorders with neurological involvement including GM1/GM2 gangliosidoses and Niemann Pick type C (NPC). Positive topline data reported earlier this year from the company’s successful Phase 2 study investigating nizubaglustat in GM2 and NPC patients demonstrated that the compound had a positive safety profile. Preliminary improvements or stabilization of clinical endpoints were observed in the majority of patients, highlighting encouraging early efficacy trends for the compound. Azafaros is preparing to initiate Phase 3 studies with nizubaglustat in GM1/GM2 gangliosidoses and NPC in Q2, 2025. About nizubaglustat Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick disease type C (NPC). Nizubaglustat has received the following designations and support: United States Food and Drug Administration (FDA) Rare Pediatric Disease Designations (RPDD) for the treatment of GM1 and GM2 gangliosidoses and NPC. Orphan Drug Designations (ODD) for GM1 and GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NPC. Fast Track Designation and IND clearance for GM1/GM2 gangliosidoses and NPC European Medicines Agency (EMA) Orphan Medicinal Product Designation (OMPD) for the treatment of for GM1 and GM2 gangliosidosis GM2 Gangliosidosis. UK Medicines and Healthcare Products Regulatory Agency (MHRA) Innovation Passport for the treatment of GM1 and GM2 gangliosidoses. About GM1 and GM2 gangliosidoses GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides respectively, in the central nervous system (CNS), resulting in progressive and severe neurological impairment and premature death. These diseases mostly affect infants and children, and no disease-modifying treatments are currently available. About Niemann-Pick disease type C (NPC) Niemann-Pick disease type C is a progressive, life-limiting neurological lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to the accumulation of various lipids, including gangliosides in the CNS. The onset of disease can happen throughout the lifespan of an affected individual, from prenatal life through adulthood. About Azafaros Azafaros is a clinical-stage company founded in 2018 with a deep understanding of rare genetic disease mechanisms using compound discoveries made by scientists at Leiden University and Amsterdam UMC and is led by a team of highly experienced industry experts. Azafaros aims to build a pipeline of disease-modifying therapeutics to offer new treatment options to patients and their families. By applying its knowledge, network and courage, the Azafaros team challenges traditional development pathways to rapidly bring new drugs to the rare disease patients who need them. Azafaros is supported by a syndicate of leading Dutch and Swiss investors including Forbion, BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital. For further information: Azafaros B.V. Email: info@azafaros.com www.azafaros.com

LEIDEN, Netherlands--( BUSINESS WIRE )--Azafaros B.V. today announced that its lead asset, nizubaglustat, has been granted orphan drug designation from regulatory authorities in both the United States and the European Union for the treatment of GM1 gangliosidosis. Additionally, the company’s Clinical Trial Application (CTA) for two global Phase 3 studies investigating the drug’s efficacy and safety in GM1/GM2 gangliosidoses and Niemann-Pick Type C (NPC) was approved by multiple European countries. Azafaros expects to initiate the two global trials in Q2, 2025. The company’s lead product is a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1/GM2 gangliosidoses and NPC. Positive topline data reported earlier this year from the company’s successful Phase 2 study investigating nizubaglustat in GM2 and NPC patients demonstrated that the compound had a positive safety profile. Preliminary improvements or the stabilization of clinical endpoints were observed in the majority of patients, highlighting encouraging early efficacy trends for the compound. The Orphan Drug Designation (ODD) and Orphan Medicinal Product Designation (OMPD) announced today cover GM1 gangliosidosis, a rare disease for which there is no current treatment available. “ We are very pleased to have been awarded orphan drug designations in both the US and EU ahead of our Phase 3 initiation planned for Q2 this year as they provide strategically important advantages in drug development – in particular during the regulatory process. With CTA approval we are set to advance the development of nizubaglustat and aim to initiate our global Phase 3 trials in GM1, GM2 and NPC in Q2, 2025,” said Stefano Portolano, Chief Executive Officer at Azafaros . “Nizubaglustat, with its dual mode of action, represents a significant leap forward compared to existing therapies and is positioned to be the first-in-class therapy for GM1 and GM2 gangliosidoses and the best-in-class therapy for NPC. Patients with these diseases have limited treatment options and we are extremely grateful to them and their families for their contribution to our clinical progress.” The orphan drug designations come after the recent promotion of Anke Arnold-Tugulu to the role of Chief Regulatory Officer at Azafaros, where she will continue to lead the company’s regulatory strategy. Commenting on the news, Dr Arnold-Tugulu said: “ These important designations are a milestone in the development of nizubaglustat. They highlight the critical need for effective treatment options for patients living with GM1 gangliosidosis, for which today no approved treatments exist, and the potential for nizubaglustat to be effective in these diseases.” Securing orphan drug designations in both the European Union and the United States offers companies valuable incentives, including market exclusivity and reduced regulatory fees, fostering innovation in treatments for rare diseases. About nizubaglustat Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick disease type C (NPC). Nizubaglustat has received the following designations and support: United States Food and Drug Administration (FDA) Rare Pediatric Disease Designations (RPDD) for the treatment of GM1 and GM2 gangliosidoses and NPC. Orphan Drug Designations (ODD) for GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NPC. IND Clearance and Fast Track Designation for GM1/GM2 gangliosidoses and NPC European Medicines Agency (EMA) Orphan Medicinal Product Designation (OMPD) for the treatment of GM2 gangliosidosis. UK Medicines and Healthcare Products Regulatory Agency (MHRA) Innovation Passport for the treatment of GM1 and GM2 gangliosidoses. About GM1 and GM2 gangliosidoses GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides respectively, in the central nervous system (CNS), resulting in progressive and severe neurological impairment and premature death. These diseases mostly affect infants and children, and no disease-modifying treatments are currently available. About Niemann-Pick disease type C (NPC) Niemann-Pick disease type C is a progressive, life-limiting neurological lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to the accumulation of various lipids, including gangliosides in the CNS. The onset of disease can happen throughout the lifespan of an affected individual, from prenatal life through adulthood. About Azafaros Azafaros is a clinical-stage company founded in 2018 with a deep understanding of rare genetic disease mechanisms using compound discoveries made by scientists at Leiden University and Amsterdam UMC and is led by a team of highly experienced industry experts. Azafaros aims to build a pipeline of disease-modifying therapeutics to offer new treatment options to patients and their families. By applying its knowledge, network and courage, the Azafaros team challenges traditional development pathways to rapidly bring new drugs to the rare disease patients who need them. Azafaros is supported by a syndicate of leading Dutch and Swiss investors including Forbion, BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital.

In addition, Azafaros will host a satellite symposium on nizubaglustat on Day 2 of the symposium, discussing nizubaglustat’s profile and plans for global Phase 3 studies Six presentations will showcase nizubaglustat’s therapeutic potential for Lysosomal Storage Disorders, including Niemann-Pick disease type C (NPC) and GM1/GM2 gangliosidoses WORLDSymposium™ 2025 takes place from February 3 to 7 in San Diego, California Leiden, Netherlands, November 19, 2024 - Azafaros B.V., a clinical-stage biotechnology company focused on rare diseases and lysosomal storage disorders, today announced that advancements with its lead asset, nizubaglustat, will feature prominently on the agenda at the upcoming WORLDSymposium™ 2025, the pre-eminent conference on lysosomal diseases. An oral presentation will highlight the results of the company’s Phase 2 RAINBOW study. Additionally, five poster presentations (one being a collaboration with patient organisations) will showcase nizubaglustat’s promise as an investigational therapy for NPC and GM1/GM2 gangliosidoses. A satellite symposium will further discuss the clinical path for the development and profile of nizubaglustat, and outline plans for pivotal Phase 3 clinical trials next year. Azafaros' presence at the conference offers a timely platform to engage key stakeholders regarding our upcoming global Phase 3 studies for GM1 and GM2 gangliosidoses, as well as NPC. These studies, set to be conducted across major regions including the United States, Europe, Latin America, and other select countries, are anticipated to commence in 2025. Oral Presentation: The RAINBOW study, a Phase 2 investigation of nizubaglustat in Niemann-Pick Type C and GM2 gangliosidosis, will be presented in an oral session on February 6. The data underscore nizubaglustat’s potential as a therapeutic option, reinforcing Azafaros’ commitment to addressing critical unmet needs in lysosomal storage disorders. Satellite Symposium on Nizubaglustat and Phase 3 Development Azafaros will host a satellite symposium on February 4 at 12:15, creating an opportunity to engage key opinion leaders, healthcare professionals and patient advocacy organizations in Azafaros’ clinical roadmap. This forum will provide insights into the results from the RAINBOW study and outline the company’s Phase 3 global development plans for nizubaglustat. Poster Presentations: February 5 Seizures: Significant co-morbidity for patients and families living with Niemann-Pick Type C: Co-authored with the UK Niemann-Pick patient group, this poster explores the significant burden seizures impose on patients and families. Nizubaglustat, a novel GCS and NLGase inhibitor, significantly increases survival in a mouse model of GM1 Gangliosidosis: Preclinical data demonstrate that nizubaglustat significantly extends survival in a GM1 mouse model, providing promising insights into its potential therapeutic effects. February 6 Gangliosidoses: Understanding disease evolution in GM1 and GM2: Data from PRONTO, the largest prospective natural history study in these diseases, enhance the understanding of disease progression in these rare lysosomal conditions. Application of a natural history study on an investigational drug in clinical development: This analysis compares data from the RAINBOW and PRONTO studies, illustrating the role of natural history studies in guiding drug development. “Fact Checking" with the Patient Community: An Industry-Advocacy Collaboration for Optimizing Trial Design: This poster is the result of a collaboration between Azafaros and two US organisations, National Tay-Sachs & Allied Diseases Association (NTSAD) and the National Niemann-Pick Disease Foundation (NNPDF), as well as two UK organisations, the CATS Foundation and NPUK. “We are honoured to present our research at such a prominent conference as the WORLDSymposium™ 2025” said Stefano Portolano, Chief Executive Officer at Azafaros. “These presentations, including the Phase 2 RAINBOW study data, reflect the promise of our late-stage asset nizubaglustat to provide a potential new therapeutic treatment to address a large unmet need for patients with certain types of lysosomal storage disorders. We look forward to highlighting important nizubaglustat data and collaborating with the medical community and patient associations dedicated to improving the lives of those impacted by these rare diseases.” About nizubaglustat Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick disease type C (NPC). Nizubaglustat has received the following designations and support: United States Food and Drug Administration (FDA) Rare Pediatric Disease Designations (RPDD) for the treatment of GM1 and GM2 gangliosidoses and NPC. Orphan Drug Designations (ODD) for GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NPC. Fast Track Designation and IND clearance for GM1 and GM2 gangliosidoses and NPC European Medicines Agency (EMA) Orphan Medicinal Product Designation (OMPD) for the treatment of GM2 gangliosidosis. UK Medicines and Healthcare Products Regulatory Agency (MHRA) Innovation Passport for the treatment of GM1 and GM2 gangliosidoses. About GM1 and GM2 gangliosidoses GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides respectively, in the central nervous system (CNS), resulting in progressive and severe neurological impairment and premature death. These diseases mostly affect infants and children, and no disease-modifying treatments are currently available. About Niemann-Pick disease type C (NPC) Niemann-Pick disease type C is a progressive, life-limiting neurological lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to the accumulation of various lipids, including gangliosides in the CNS. The onset of disease can happen throughout the lifespan of an affected individual, from prenatal life through adulthood. About Azafaros Azafaros is a clinical-stage company founded in 2018 with a deep understanding of rare genetic disease mechanisms using compound discoveries made by scientists at Leiden University and Amsterdam UMC and is led by a team of highly experienced industry experts. Azafaros aims to build a pipeline of disease-modifying therapeutics to offer new treatment options to patients and their families. By applying its knowledge, network and courage, the Azafaros team challenges traditional development pathways to rapidly bring new drugs to the rare disease patients who need them. Azafaros is supported by a syndicate of leading Dutch and Swiss investors including Forbion, BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital. For further information: Azafaros B.V. Email: info@azafaros.com www.azafaros.com